Printed Poster | Session 2
076 – Social defeat stress induces expression of cyclooxygenase-2 and prostaglandin production in reactive brain endothelia
Wenyuan Yin (1) – Anzela Niraula (1) – Caroline Sawicki (2) – Daniel McKim (1) – Jonathan Godbout (1) – John Sheridan (2)
The Ohio State University, Department of Neuroscience, Columbus, United States (1) – The Ohio State University, Division of Biosciences, Columbus, United States (2)
Repeated social defeat (RSD) is a murine model of psychosocial stress that causes neuronal and microglial activation, peripheral monocyte recruitment to the brain, and anxiety-like behavior. Previous studies have demonstrated that activation of neurons and endothelial cells in regions associated with threat appraisal is necessary for monocyte trafficking and the development of anxiety-like behavior following RSD. Monocytes that are recruited from the periphery express interleukin-1 (IL-1) beta and selectively interact with the reactive endothelium. Activated endothelia express higher levels of interleukin-1 receptor 1 (IL-1R1), adhesion molecules, and cyclooxygenase-2 (COX-2). In the current study, we sequenced actively translated mRNA from endothelial cells using a RiboTag approach to further characterize the reactive endothelium that develops after RSD. This approach corroborated previous findings including increased translation of IL-1R1, E-selectin, P-selectin, and prostaglandin-related proteins such as COX2 and Slco2a1. The translational changes are consistent with activation of the Nuclear Factor kappa B signaling pathway, which is downstream of IL-1 signaling. Previous reports indicate that prostaglandins, specifically PGE2, may be involved in behavioral changes after social defeat stress. Ongoing studies will determine whether PGE2 is increased specifically in regions of the brain associated with threat appraisal and anxiety after RSD. Next, we will determine if systemic pretreatment with SC-236, a selective COX-2 inhibitor, prevents the development of anxiety-like behavior after RSD. Finally, we will assess how inhibition of COX-2 impacts neuronal activation, microglia activation, and peripheral monocyte recruitment after stress. Targeting COX-2 in brain endothelia may be a promising therapeutic approach for future treatments of anxiety disorders.